We have been studying allergic encephalomyelitis (EA) in juvenile guinea pigs which undergo a chronic stage after an acute attack or silent acute stage characterized by histological changes in the CNS without clinical signs. Using monoclonal antibodies against guinea pig T cells and antibodies against immunoglobulins, T and B cells were traced to their CNS sites. In acute EAE, T cells appeared before B cells and were distributed within the white matter parenchyma while B cells remained in perivascular spaces. In chronic EAE which is reminiscent of multiple sclerosis in man, T cells were also localized within the parenchyma. B cell infiltrates were more extensive than in acute EAE, and although most were centered around blood vessels, some were in the parenchyma. In chronic EAE treated with myelin basic protein (MBP), disease was arrested, and T and B infiltrates in the white matter negligible. In other studies on treatment of chronic EAE, marked clinical improvement was noted when a lipid hapten of myelin, galactocerebroside (GC) was added to the MBP. The rationale stemmed from work suggesting that MBP was responsible for sensitization of T cells and GC was important in producing demyelinating antibodies, and possibly both were important in the production of disease.